Pancreatic cancer is a tumor that develops at the retroperitoneal space, a position clinically difficult to be detected. Thus, conventionally, it was often found at a stage when treatment is difficult, and was considered an intractable tumor. Diagnostic methods have made a great progress due to diagnostic imaging such as US, CT and MRI, and endoscopy based on recent technological innovation. Despite these advances in diagnostic methods, treatment results of pancreatic cancer have been below expectations. Excision rates and prognosis of tumors 2 cm or larger are both poor, and rates of discovery are low for cases of small pancreatic cancers (T1) 2 cm or smaller with better excision rates, and, for the cases that were detected, Stage I cases account for less than 50% with the half or more already being at the stage of advanced cancer. In order to enhance the treatment results of this pancreatic cancer, it is important to discover small cancers at early stages.
For the early discovery of pancreatic cancer, early diagnosis of pancreatic cancer is important, and diagnostic methods for detecting pancreatic cancer at present include the above-mentioned diagnostic imaging such as US, CT and MRI, and measurement of serum enzymes and tumor markers. The measurement of serum enzymes and tumor markers is very important for the discovery of pancreatic cancer, but lacks cancer specificity because pancreatic enzymes in the blood increase with the inflammation of the pancreas.
Furthermore, though a sugar chain antigen such as CAl9-9, a tumor marker, is useful as a marker for the diagnosis and monitoring of progressive pancreatic cancer, its usefulness in early diagnosis is not satisfactory. In addition to CAl9-9, it has been reported, CEA, ST-439, sialyl SSEA-1 (SLX), DU-PAN-2, CA-125, CA-50 etc. are useful as tumor markers; all of them, however, are sugar chain antigens, and are not substances specifically secreted from a cancer of the pancreas. The problem, therefore, is the low specificity of markers for pancreatic cancer.
Conventionally, tumor markers specific for certain tumors have been isolated and identified from the serum of cancer patients and cells established from cancer tissues. For such isolation and identification, these potential marker substances had to be obtained in large quantities, and a large quantity of samples was needed, from which trace amounts of markers had to be detected. Thus, it was only possible to detect substances that are present in large quantities in test samples.
Peptides or low molecular weight proteins selectively secreted from cancer cells could serve as tumor markers. This hypothesis became a reality when the present inventors demonstrated that gastrin-releasing peptide precursor (proGRP) is useful as a tumor marker specific for small cell lung carcinoma (SCLC) [Miyake et al., Cancer Res. 54:2136-2140 (1996)]. The present inventors have studied the production of a series of peptides by radioimmunoassay (RIA), and demonstrated that GRP is selectively recognized in SCLC [Yamaguchi et al., Recent Results Cancer Res. 99:107-116 (1985)].
By determining proGRP, a precursor of GRP, the present inventors demonstrated that it can be used as a marker for early detection of SCLC and for therapeutic effects, which have been granted patents (U.S. Pat. No. 2,925,479, U.S. Pat. No. 3,210,994). However, the method that discovered the usefulness of this proGRP as a tumor marker is one in which sera of patients with SCLC and sera of patients with non-SCLC are measured by RIA, and thus it is necessary to generate many different antibodies and to carry out the determination of a multitude of samples, requiring a large amount of time and effort. In addition, new peptide candidates cannot be found by this method.